s team at the University of Virginia are employing a novel approach to design, test and implement progressive improvements of artificial pancreas software based on a modular architecture concept. This approach would allow the various components, such as a software module focused on avoiding hypoglycemia or one that keeps glucose within a target range, to be seamlessly integrated in systems that can be implemented and tested in a stepwise fashion in clinical studies. The advantages of this module-based approach were demonstrated in two inpatient clinical trials. Each trial used software packages in which different modules were used: a standard control to range software module (sCTR) and a more sophisticated enhanced control to range (eCTR) software module. Both inpatient trials compared sCTR and eCTR vs. standard pump therapy and included meals, overnight rest and 30 minutes of exercise. The studies were conducted in 11 adolescents and 27 adults with T1D at the Universities of Virginia, Padova and Montpellier. sCTR was found to significantly increase the time spent in the normal blood glucose range while reducing hypoglycemia. eCTR was found to further improve mean blood glucose from 139 to 120 mg/dl without increasing hypoglycemia and reduced variability overnight. In addition to demonstrating improved glucose control and reduced hypoglycemia with both sCTR and eCTR these studies highlighted the efficient use of modules in the design, testing and implementation of artificial pancreas algorithms.

Ramifications for Individuals with Type 1 Diabetes:

The modular approach described by Drs. Marc Breton and Boris Kovatchev has accelerated the development and testing of control-to-range artificial pancreas software by facilitating the stepwise development and testing of discrete software modules. Control-to-range systems are now being tested in outpatient pilot studies and a larger pivotal trial to assess efficacy is in the planning stages for 2013. Most importantly, these systems can be developed with todays available technologies, and set the stage for the development of future generation AP systems and advanced devices.

JDRF Involvement:

JDRF funded this research through a grant to Dr. Boris Kovatchev at the University of Virginia. Dr. Kovatchev is a member of the JDRF Artificial Pancreas Consortium.

a major step forward. Furthermore, previous research has shown that people who have hypoglycemia unawareness can become aware again of low blood sugars by avoiding frequent lows. Preventing all lows for two weeks resulted in increased symptoms of a low blood sugar and a return to nearly normal symptoms after 3 months. A pump that suspends insulin delivery when glucose levels fall to a pre-set low threshold may provide significant benefit to individuals who have hypoglycemia unawareness. This study suggests that LGS is safe and unlikely to result in adverse outcomes in this patient population. At the conclusion of this ongoing study we will better understand the potential utility of LGS in preventing hypoglycemia unawareness and whether it can prevent loss of the critical warning symptoms in individuals who suffer from this T1D complication. The Veo System is not currently approved for use in the US.

JDRF Involvement:

Dr. Trang Ly is the recipient of a JDRF postdoctoral fellowship and Dr. Tim Jones, her mentor, is receiving JDRF funding to assess biochemical measures of hypoglycemia unawareness in a subset of the participants in this trial. Dr. Tim Jones is a member of the JDRF artificial pancreas consortium.

The Accuracy Benefit of Multiple Amperometric Glucose Sensors in People with Type 1 Diabetes, Diabetes Care Publish Ahead of Print, published online February 22, 2012.

Ramifications for Individuals with T1D:

The successful development and delivery of fully automated closed loop artificial pancreas systems to individuals with T1D will require significant improvements in CGM accuracy and reliability. Employing multiple redundant CGM sensors may be an important strategy to achieve these objectives.

JDRF Involvement:

This work was supported by grants from The Helmsley Charitable Trust, HEDCO Foundation and by the JDRF Artificial Pancreas Project.